This invention relates to the field of separation science, analytical biochemistry, mass spectrometry, and biosensors.
The embodiments of this invention have applications in biology and medicine, including analysis of gene functions, differential gene expression, protein discovery, cellular and clinical diagnostics, food product research and quality assurance, pathogen analysis, environmental analysis, drug discovery, toxicology and drug screening.
In the filed of analytical chemistry, a technique that has demonstrated impressive development and popularity during the past decades involves the use of Time-of-Flight Mass Spectroscopy (“TOFMS”). As is the case with most mass spectrometers, a TOFMS system consists of two major components: an ionization source, which corresponds with the sample introduction means; also known as the interface or inlet system and the mass analyzer, which corresponds with the mass measurement and the ion detection portion. The sample introduction system in a laser desorption/ionization TOFMS is configured to receive a sample probe, which introduces the sample into the mass spectrometer. Biochips, protein biochips or ProteinChip® arrays are all examples of different types of sample probes.
While mass spectroscopy has gained popularity in the analytical biochemistry arena, most analysts have focused their skills towards adapting their sample introduction systems and sample probes to fit a particular mass spectrometer's requirements. This approach tends to constraint the analysts to do what is doable, as opposed to allowing the analyst to do what can be done using a mass spectrometer. In a sense, current mass spectroscopy based analytical techniques start from the mass analyzer, and thus impose their constraints on the sample introduction system and the sample probe. So, while many advances have been made in other analytical areas, such as microfluidic-enabled devices, surface scanners and chromatography, these advances have not found their way into the current generation of sample probes and mass spectroscopy systems.
In addition to these problems, the currently available biochip technologies suffer from various limitations, including: the problems associated with the open loop preparation of samples such as slow methods development and poor assay reliability; excessive sample loss due to the loss of analyte to wetted surfaces encountered during sample preparation; and requiring relatively large amounts of precious analytes. In addition to these, other problems of existing analytical techniques include, low resolution, chromatographic separation primarily based upon solid phase extraction, which characteristically has only a single plate of chromatographic resolution, as well as their limited applicability to biomolecular studies, limited throughput, and their not being directly amenable to automation, since most of the preparation and processing is carried out in an open loop manner.
Embodiments of the current invention address these and other problems.